Panel A shows a structural diagram of a full-length AMPAR and a close-up of the Rat-GluA2 ligand-binding domain. The close-up highlights specific residues, T501 and R506, interacting with glutamate. Panel B presents an amino acid sequence alignment of selected ligand-binding residues from various receptor subunits, with Rat-GluA2 residues in bold. Panels C to F display line graphs of mean normalized current responses to increasing concentrations of glutamate for different AMPAR subunit combinations and mutations. The x-axes represent glutamate concentration in molars (M), and the y-axes represent normalized current (I/Imax). Each graph includes data points for wild-type and mutant subunits, with standard deviations and sample sizes indicated. Panel G shows a scatter plot of pEC50 values derived from the experiments in Panels C to F. The x-axis lists different subunit combinations and mutations, while the y-axis represents glutamate pEC50 values. Statistical significance is indicated by asterisks, comparing wild-type to mutants and homologous mutations in other subunits.
Novel subunits make different functional contributions to heteromeric AMPARs. (A) Full-length AMPAR (left, PDB accession no. 5WEO [Twomey et al., 2017]) and Rat-GluA2 LBD X-ray structure (right, PDB accession no. 1FTJ [Armstrong and Gouaux, 2000]). (B) Selected Rat-GluA2 ligand-binding residues (bold) aligned with other receptor subunits (full alignment in Fig. S4). (C–F) Mean (±SD, n in brackets in legends) normalized (to maximum in each recording) current responses to increasing concentrations of glutamate for indicated AMPAR subunit combinations (mutations in superscript). (G) pEC50 values from experiments in C–F. WT and cognate mutants were compared with one-way ANOVA and Tukey’s multiple comparisons test, where *P < 0.05, **P < 0.01, and ***P < 0.001 compared with WT (black asterisks) or compared with homologous mutation in other subunit (red asterisks). n values shown in parentheses in C–F.